Method for producing tablets from plant extracts

ABSTRACT

In a method for the production of tablets from plant extracts such as St. John&#39;s wort extract with an extract content of 80%, the extract treated on a conveyor dryer is compacted after adding 1% of silicon dioxide, and a granulate with a defined particle size distribution and therefore a defined surface area is produced from the compactate. To achieve a high rate of decomposition and active agent release with a low adjuvant content and high extract content, a combination of blasting agents including sodium hydrogencarbonate and two other, lower-dosed blasting agents such as croscarmellose sodium and sodium carboxymethyl starch—among other adjuvants—is added. The method results in a tablet suitable for oral administration containing 900 mg of St. John&#39;s wort extract.

[0001] This invention relates to a method for producing tablets from plant extracts, in particular, St. John's wort extract, in which a dry extract mixed with adjuvants is compacted and granulated and the extract compactate particles are masked with moisture protecting, surface smoothing, and separating agents are pressed into tablets together with other adjuvants.

[0002] Drugs in tablet form made from plant extracts are characterized by a more targeted release and more accurate dosing of the pharmaceutically effective ingredients as compared to liquid forms of application, which permits improved therapy control.

[0003] However, the forms of application of drugs made from plant extracts known as yet are necessary because a high portion of adjuvants is required both for the production process as well as for fast release of the active ingredients, rendering the active ingredient portion that can be put into a tablet with a limited volume to be suitable for oral administration comparatively small.

[0004] Using the above-mentioned method known from DE 199 57 472 A1, a tablet sized for oral administration with a St. John's wort extract can be produced in which the extract portion amounts to 65% or about 600 mg; this is mainly achieved by coating homogeneously sized particles of the extract compactate that was formed with a high content of adjuvants with titanium dioxide, talc, and highly dispersed silicon dioxide. Coating the granulate with the adjuvants mentioned last ensures protection against moisture required for good flow behavior, homogeneous mixing with other adjuvants and a smooth surface of the compactate particles to keep the content of other adjuvants low during mixing and coating and to be able to put a high extract content into a single tablet. Another desirable increase of the extract content during tablet production is encountering segregation or prepressing problems, or yields cores that are sensitive to moisture or too solid. In addition, keeping to the specified times for tablet decomposition and active ingredient release into the body is difficult if the active ingredient content is increased any further.

[0005] The main problem of producing tablets that have an extract content as high as possible and an accordingly low adjuvant content therefore is to ensure faultless tabletting and fast release of the active pharmaceutical ingredients.

[0006] It is therefore the problem of this invention to provide a method that prevents tabletting problems caused by segregation or decomposition due to moisture and enables the production of a tablet formed of plant extracts whose extract content is considerably increased as compared to known solid forms of application of this type and which has good decomposition and release properties.

[0007] This problem is solved according to the invention by a method comprising the characteristics described in claim 1.

[0008] Other characteristics and embodiments of the invention are described in the subclaims.

[0009] According to a first characteristic, the inventive idea is that the extract that is preferably dried on a conveyor dryer is compacted, i.e. pressed, using highly dispersed silicon oxide that also acts as a separating agent. According to a second characteristic of the invention, the extract compactate particles are bigger and thus have a reduced surface as compared to known methods to keep the adjuvant content required for masking the extract compactate particles to protect them against moisture and to improve their pressing behavior and decomposition properties low. A predefined particle size distribution is set to reduce the overall surface area of the extract compactate particles by screening these particles and allowing only specific particle sizes in specific quantities to pass on to the subsequent tabletting process. In order to meet the fast decomposition requirements with a tablet containing a high dose of plant extracts and a small portion of adjuvants, an adjuvant combination of three blasting agents is added according to yet another characteristic of the invention, one of which consisting of sodium hydrogencarbonate and exceeding the portion of the two other blasting agents by a multiple.

[0010] The essence of the invention therefore is the combination of adding a low percentage of highly dispersed silicon dioxide as early as prior to compacting, reducing the overall surface area of the extract compactate particles by a defined particle size distribution, and using sodium hydrogencarbonate in conjunction with two other, significantly lower dosed blasting agents.

[0011] It is this combination of characteristics that makes it possible to produce, without tabletting problems, a tablet of an acceptable size with a low adjuvant content and a high extract content of about 80% that decomposes sufficiently fast in the body and meets the requirements of fast release.

[0012] One aspect of the invention is that the reduced extract is dried in a vacuum on a conveyor dryer. The percentage of silicon dioxide intermixed with the dry extract is only 1%. The extract compactate particles are masked in a known way with titanium dioxide and talc for moisture protection and surface smoothing.

[0013] According to another important characteristic of the invention, the surface area of the extract compactate particles is reduced as compared to known methods, which in combination with the blasting agents used according to the invention ensure the aimed decomposition of the tablet with a high dosage of herbal active ingredients, and a particle size distribution is set wherein at least 99% are smaller than 1,000 μm, at least 90% are smaller than 710 μm, 40% to 80% are smaller than 500 μm, 30% to 60% are smaller than 250 μm, and a maximum of 40% are smaller than 125 μm. This particle size distribution defines a particle surface with which the adjuvant portion for coating the particles can be further reduced.

[0014] According to yet another characteristic of the invention, the combination of blasting agents for the specified particle size distribution/surface area of the extract compactate particles is 5% to 15% of sodium hydrogencarbonate and 0.5% to 5% each of croscarmellose sodium and sodium carboxymethyl starch. At the concentrations specified, other common blasting agents such as starch derivatives, cellulose compounds, or polyvinyl pyrrolidone may also be used in combination with sodium hydrogencarbonate. The desired decomposition times are only achieved by the synergic effect of the blasting agents used in the combination at the specified limited quantity in relation to the overall adjuvant quantity. According to the invention, dry compacting or fluidized-bed granulation steps can be included in the process.

[0015] A method for producing film tablets with St. John's wort as the active ingredient that exemplifies the invention is described in greater detail below.

[0016] A liquid extract of St. John's wort buds and flowers produced using an ethanol-water mixture is filtered and reduced by approx. 60% by drying under reduced pressure at 40° to 60° C. The reduced extract is then subjected to high-temperature treatment (15 seconds at 140° C.) to reduce germs and to gentle conveyor drying under reduced pressure at temperatures between 30° and 60° C.

[0017] In a subsequent step, 1% of highly dispersed silicon dioxide is added to the St. John's wort extract as an adjuvant for the following compacting step, and the extract particles are coated with the silicon dioxide in a mixing process. Finally the extract prepared in this way is mechanically pressed into a compactate and comminuted in a blending drum. The mixture of compacted extract compactate particles is screened, and cruder particles are selected for further processing into tablets to reduce the overall surface area. The particle size distribution is set so that at least at least 99% are smaller than 1,000 μm, at least 90% smaller than 710 μm, 40% to 80% smaller than 500 μm, 30% to 50% smaller than 250 μm, and a maximum of 40% smaller than 125 μm. The resulting bulk density of the extract particles selected for further processing is in the range from 0.63 to 0.80 g/ml and a compacted bulk density of 0.73 to 0.85 g/ml.

[0018] The extract compactate particles in the specified particle size distribution are masked with titanium dioxide, talc, and vegetable magnesium stearate and additionally coated with sodium hydrogencarbonate, croscarmellose sodium, and sodium carboxymethyl starch. Subsequently, the extract compactate particles that were intermixed with the specified adjuvants are pressed into tablets with an overall weight of 1090 mg using a tablet press; the St. John's wort content in such tablet is 900 mg while the tablet dimensions (9.5 mm in width, 20.5 mm in length, and 6.6 mm in height) make it suitable for oral administration. The tablet cores are then coated with a primer and a color enamel. 

1. A method for producing tablets from plant extracts, in particular, St. John's wort extract, in which a dry extract mixed with adjuvants is compacted and granulated and the extract compactate particles are masked with moisture protecting, surface smoothing, and separating agents are pressed into tablets together with other adjuvants, characterized in that the compacting step is carried out using only highly dispersed silicon dioxide that acts as a separating agent, in that extract compactate particles are selected for further processing in defined stepped particle sizes and a particle size distribution aimed at achieving a small overall granulate surface area, and in that the particles are coated with an additional combination of blasting agents consisting mainly of sodium hydrogencarbonate and two other lower-dosed blasting agents.
 2. The method according to claim 1, characterized in that the percentage of silicon dioxide added prior to compacting is 1%.
 3. The method according to claims 1 and 2, characterized in that the particle size of the extract compactate particles selected for further processing is approximately between 125 μm and 1,000 μm.
 4. The method according to claim 1, characterized in that a particle size distribution is selected where at least 99%<1,000 μm, at least 90%<710 μm, 40% to 80%<500 μm, 30% to 60%<250 μm and a maximum of 40%<125 μm.
 5. The method according to claim 4, characterized in that the bulk density of the extract compactate particles that can be achieved due to the particle size distribution is in the range from 0.63 to 0.80 g/ml and the compacted bulk density is in the range from 0.73 to 0.85 g/ml.
 6. The method according to claim 1, characterized in that the percentage of sodium hydrogencarbonate as a blasting agent is between 5% and 15% while the percentage of each of the other two blasting agents combined with it is between 0.5% and 5%.
 7. The method according to claim 6, characterized in that croscarmellose sodium and sodium carboxymethyl starch are used as other blasting agents in combination with sodium hydrogencarbonate.
 8. The method according to claim 6, characterized in that starch derivatives, cellulose compounds, or polyvinyl pyrrolidones are used as other blasting agents in combination with sodium hydrogencarbonate.
 9. The method according to any one of claims 1 through 8, characterized in that vegetable magnesium stearate is added to the extract compactate particles as another adjuvant.
 10. The method according to claim 1, characterized in that the reduced extract is dried in a vacuum conveyor drying process.
 11. The method according to claim 1, characterized in that talc and titanium dioxide are added as masking adjuvants to the particle mixture for surface smoothing and protection against moisture. 